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A comparison of josamycin with macrolides and related antibiotics on isolated rat atria
Abstract:
The effects of macrolide (Josamycin, erythromycin, spiramycin and oleandomycin) and related antibiotics (clindamycin and lincomycin) were examined and compared in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of rats. Josamycin and erythromycin (10(-7)-10(-4) M) produced a dose-dependent decrease in rate. contractile force and maximum following frequency and prolonged the sinus node recovery time and the refractory period. The negative inotropic effect of josamycin was not modified by pretreating the atria with atropine or with a mixture of antagonists containing phentolamine, practolol, diphenhydramine, cimetidine, methysergide and indomethacin. In isolated right atria, josamycin did not block the positive inotropic and chronotropic responses to isoprenaline but shifted the dose-response curve to Ca to the right. Josamycin and erythromycin reduced in a dose-dependent manner the slow responses induced in K-depolarized right atria by isoprenaline but this effect was reversed by increasing the Ca concentration in the bathing media. These findings demonstrate a direct negative inotropic effect of josamycin and suggest that this effect could in some way be explained by inhibiting transmembrane Ca influx into atrial cells. The clinical significance of these results is discussed.
Insights
Macrolide antibiotics like josamycin and erythromycin directly decrease heart atrial contractility and rate. Their negative inotropic effects may stem from inhibiting calcium influx into atrial cells.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Macrolide and related antibiotics are widely used.
- Their direct effects on cardiac function require further elucidation.
Purpose of the Study:
- To compare the cardiac effects of macrolides (josamycin, erythromycin, spiramycin, oleandomycin) and related antibiotics (clindamycin, lincomycin).
- To investigate the mechanism of the negative inotropic effect of josamycin.
Main Methods:
- Isolated rat right and left atrial preparations were used.
- Dose-dependent effects on rate, contractile force, and electrophysiology were measured.
- Specific receptor antagonists and calcium concentration were manipulated.
Main Results:
- Josamycin and erythromycin exhibited dose-dependent negative inotropic and chronotropic effects.
- Josamycin's negative inotropic effect was independent of common receptor pathways.
- Josamycin and erythromycin inhibited isoprenaline-induced slow responses, reversible by increased calcium.
Conclusions:
- Josamycin and erythromycin exert direct negative inotropic effects on atrial preparations.
- This effect is likely mediated by inhibition of transmembrane calcium influx.
- The findings suggest potential clinical implications for patients with cardiac conditions.